Search Results (8)

Background: Stereotactic Radiotherapy (SRT) in pancreatic and biliary tract cancer (PBC) suffers from proximity to any organ(s) at risk (OARs). Some strategies to manage this issue have previously been proposed, such as Simultaneous Integrated Protection (SIP), with the aim of maintaining a biological effective dose prescription while reducing toxicities. We performed a systematic review of the literature about SRT techniques applied in patients with tumor in proximity to OARs, with the aim of testing safety and efficacy. Methods: using PRISMA guidelines, we selected studies from a pool of more than 25,000 articles published from 2010 to 30 January 2023 that explored the use of SRT to deliver targeted treatment for PBC. We then selected the ones referring to decreases in prescription doses (for SRT only) in the area of overlap between planning target volume (PTV) and OARs. Local control (LC) and toxicities being detailed were exclusion criteria for articles. Results: 9 studies were included in our review, considering 368 patients. One-year LC probability ranges between 67% and 98.3% were reported. Late G3 toxicities ranged between 0% and 5.3%, while G4-G5 late toxicities were both reported as 0.3%. Conclusion: prioritizing critical OAR constraints limits severe toxicities while preserving LC in PBC SRT. Improving in-study reporting is essential to confirm these promising results. Full article

In pediatric rhabdomyosarcoma (RMS), elevated Akt signaling is associated with increased malignancy. Here, we report that expression of a constitutively active, myristoylated form of Akt1 (myrAkt1) in human RMS RD cells led to hyperactivation of the mammalian target of rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (p70S6K) pathway, resulting in the loss of both MyoD and myogenic capacity, and an increase of Ki67 expression due to high cell mitosis. MyrAkt1 signaling increased migratory and invasive cell traits, as detected by wound healing, zymography, and xenograft zebrafish assays, and promoted repair of DNA damage after radiotherapy and doxorubicin treatments, as revealed by nuclear detection of phosphorylated H2A histone family member X (γH2AX) through activation of DNA-dependent protein kinase (DNA-PK). Treatment with synthetic inhibitors of phosphatidylinositol-3-kinase (PI3K) and Akt was sufficient to completely revert the aggressive cell phenotype, while the mTOR inhibitor rapamycin failed to block cell dissemination. Furthermore, we found that pronounced Akt1 signaling increased the susceptibility to cell apoptosis after treatments with 2-deoxy-D-glucose (2-DG) and lovastatin, enzymatic inhibitors of hexokinase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), especially in combination with radiotherapy and doxorubicin. In conclusion, these data suggest that restriction of glucose metabolism and the mevalonate pathway, in combination with standard therapy, may increase therapy success in RMS tumors characterized by a dysregulated Akt signaling. Full article

Background and purpose: Although chemotherapy, biological agents, and radiotherapy (RT) are cornerstones of the treatment of multiple myeloma (MM), the literature regarding the possible interactions of concurrent systemic treatment (CST) and RT is limited, and the optimal RT dose is still unclear. Materials and methods: We retrospectively analyzed the records of patients who underwent RT for MM at our institution from 1 January 2005 to 30 June 2020. The data of 312 patients and 577 lesions (treated in 411 accesses) were retrieved. Results: Most of the treated lesions involved the vertebrae (60%) or extremities (18.9%). Radiotherapy was completed in 96.6% of the accesses and, although biologically effective doses assuming an α/β ratio of 10 (BED 10) > 38 Gy and CST were significantly associated with higher rates of toxicity, the safety profile was excellent, with side effects grade ≥2 reported only for 4.1% of the accesses; CST and BED 10 had no impact on the toxicity at one and three months. Radiotherapy resulted in significant improvements in performance status and in a pain control rate of 87.4% at the end of treatment, which further increased to 96.9% at three months and remained at 94% at six months. The radiological response rate at six months (data available for 181 lesions) was 79%, with only 4.4% of lesions in progression. Progression was significantly more frequent in the lesions treated without CST or BED 10 < 15 Gy, while concurrent biological therapy resulted in significantly lower rates of progression. Conclusion: Radiotherapy resulted in optimal pain control rates and fair toxicity, regardless of BED 10 and CST; the treatments with higher BED 10 and CST (remarkably biological agents) improved the already excellent radiological disease control. Full article

Imines or Schiff bases (SB) are formed by the condensation of an aldehyde or a ketone with a primary amine, with the removal of a water molecule. Schiff bases are central molecules in several biological processes for their ability to form and cleave by small variation of the medium. We report here the controlled hydrolysis of four SBs that may be applied in the fragrance industry, as they are profragrances all containing odorant molecules: methyl anthranilate as primary amine, and four aldehydes (cyclamal, helional, hydroxycitronellal and triplal) that are very volatile odorants. The SB stability was assessed over time by HPLC-MS in neutral or acidic conditions, both in solution and when trapped in low molecular weight gels. Our results demonstrate that it is possible to control the hydrolysis of the Schiff bases in the gel environment, thus tuning the quantity of aldehyde released and the persistency of the fragrance. Full article

The three gelators presented in this work (Boc-D-Phe-L-Oxd-OH F0, Boc-D-F₁Phe-L-Oxd-OH F1 and Boc-D-F₂Phe-L-Oxd-OH F2) share the same scaffold and differ in the number of fluorine atoms linked to the aromatic ring of phenylalanine. They have been applied to the preparation of gels in 0.5% or 1.0% w/v concentration, using three methodologies: solvent switch, pH change and calcium ions addition. The general trend is an increased tendency to form structured materials from F0 to F1 and F2. This property ends up in the formation of stronger materials when fluorine atoms are present. Some samples, generally formed by F1 or F2 in 0.5% w/v concentration, show high transparency but low mechanical properties. Two gels, both containing fluorine atoms, show increased stiffness coupled with high transparency. The biocompatibility of the gelators was assessed exposing them to fibroblast cells and demonstrated that F1 and F2 are not toxic to cells even in high concentration, while F0 is not toxic to cells only in a low concentration. In conclusion, the presence of even only one fluorine atom improves all the gelators properties: the gelation ability of the compound, the rheological properties and the transparency of the final materials and the gelator biocompatibility. Full article

Olfactory neuroblastoma (ONB) is a rare sinonasal neoplasm with a peculiar behavior, for which limited prognostic factors are available. Herein, we investigate the transcriptional pathways altered in ONB and correlate them with pathological features and clinical outcomes. We analyze 32 ONB patients treated with curative intent at two independent institutions from 2001 to 2019 for whom there is available pathologic and clinical data. We perform gene expression profiling on primary ONB samples and carry out functional enrichment analysis to investigate the key pathways associated with disease-free survival (DFS). The median age is 53.5 years; all patients undergo surgery and a pure endoscopic approach is adopted in the majority of cases (81.2%). Most patients have advanced disease (stages III–IV, 81.2%) and 84.4% undergo adjuvant (chemo)radiotherapy. The median follow-up is 35 months; 11 (26.8%) patients relapse. Clinical characteristics (gender, stage and Hyams’ grade) are not associated with the outcomes. In contrast, TGF-beta binding, EMT, IFN-alpha response, angiogenesis, IL2-STAT5 and IL6-JAK-STAT3 signaling pathways are enriched in patients experiencing recurrence, and significantly associated with shorter DFS. Clustering of transcriptional profiles according to pathological features indicates two distinct molecular groups, defined by either cytokeratin-positive or -negative immunostaining. Definition of the characterizing ONB transcriptomic pathways may pave the way towards tailored treatment approaches. Full article

Physical hydrogels are supramolecular materials obtained by self-assembly of small molecules called gelators. Aromatic amino acids and small peptides containing aromatic rings are good candidates as gelators due to their ability to form weak bonds as π-π interactions and hydrogen bonds between NH and CO of the peptide chain. In this paper we show our results in the preparation of a transparent hydrogel that was obtained by self-assembly of a fluorine-containing dipeptide that relies on the additional formation of halogen bonds due to the fluorine atoms contained in the dipeptide. We used Boc-D-F₂Phe-L-Oxd-OH (F₂Phe = 3,4-difluorophenylalainine; Oxd = 4-methyl-5-carboxy-oxazolidin-2-one) that formed a strong and transparent hydrogel in 0.5% w/w concentration at pH = 4.2. The formation of a hydrogel made of unnatural fluorinated amino acids may be of great interest in the evaluation of patients with parkinsonian syndromes and may be used for controlled release. Full article

Anticancer treatment efficacy is limited by the development of refractory tumor cells characterized by increased expression and activity of mechanisms promoting survival, proliferation, and metastatic spread. The present review summarizes the current literature regarding the use of the anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with a focus on cells resistant to approved therapies, including so called “cancer stem cells”. Mebendazole meets many of the characteristics desirable for a repurposed drug: good and proven toxicity profile, pharmacokinetics allowing to reach therapeutic concentrations at disease site, ease of administration and low price. Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters. Mebendazole not only exhibits direct cytotoxic activity, but also synergizes with ionizing radiations and different chemotherapeutic agents and stimulates antitumoral immune response. In vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival. Further investigations are warranted to confirm the clinical anti-neoplastic activity of MBZ and its safety in combination with other drugs in a clinical setting. Full article